Colorectal cancer (CRC) is the third most common cancer and the fourth cause of cancer-related deaths worldwide. Each year, almost one and a quarter million new cases of colorectal cancer are diagnosed and over six hundred thousand deaths are attributable to this disease (Ferlay et al., 2010). Its incidence and difficult early diagnosis make CRC a primary focus in the oncology community. CRC is often diagnosed after symptoms appear, but most people with early disease are symptomless and symptoms usually appear only with more advanced disease. Therefore, 30 to 40% of CRC patients have metastatic disease at diagnosis (Benson, 2007). The overall survival rate of patients with metastatic colorectal cancer at 5 years is less than 10%. In contrast, up to 80% of patients can be cured by tumor resection if the CRC is detected at an early stage (Benson, 2007). Therefore, early diagnosis is important for the proper control of CRC. Although colonoscopic screening for CRC is currently the most reliable screening tool, the invasive nature and the incurred cost have hampered the wide application of this procedure. On the other hand, the fecal occult blood testing is a non-invasive alternative. However, it lacks the sensitivity and specificity required for an effective screening tool and requires meticulous dietary restriction.
Unfortunately, current therapeutic approaches also lack efficacy to successfully cure the disease, especially in patients with metastatic CRC. Therefore, much effort is needed to optimize the treatment of CRC. In 2004, the U.S. Food and Drug Administration (FDA) approved bevacizumab (AVASTIN®), a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), in combination with classic chemotherapy as a first line treatment for CRC. However, the phase 3 clinical trial revealed that this combination therapy only adds less than 5 months to the overall survival of CRC patients (Hurwitz et al., 2004).
Thus, there is a pressing need to identify specific non-invasive biomarkers for CRC early diagnosis and monitoring, in order to avoid the more advanced stages of the disease that are difficult to cure. Such early, non-invasive biomarkers would in fact be useful for several other tumor types as well.